DermiSphere?: An Advanced Dermal Regeneration Scaffold for Reconstructive Surgery ABSTRACT On its own, the human body is incapable of dermis regeneration. If not properly treated, large full-thickness skin wounds (loss of dermis) heal through contraction of surrounding skin and scar formation, which may ultimately lead to chronic wound formation, permanent damage, disability, disfigurement and patient suffering. For years, the autologous tissue transfer (a patient serving as their own donor) has been the gold-standard treatment for this type of wound, but lack of surgical expertise, poor donor site availability and significant donor-site morbidity severely limit its application. In the early 2000s, alternative, ?off the shelf? neo-dermis formation treatments emerged, which now have annual sales between $500 million to $1 billion, growing 8- 12% annually. The leading product by sales, Integra?, possesses shortcomings in its time to heal and is ineffective in many types of full thickness wound scenarios. DermiSphere?, the proposed product of this SBIR Phase I application will be an implantable scaffold that rapidly restores patients? functional dermis. DermiSphere?s patented three-dimensional microscopically patterned architecture guides rapid cell penetration from the wound bed into the scaffold matrix, leading to rapid vascularization and neo-dermal tissue formation. Our murine studies to date demonstrate DermiSphere?s superior invasion and neovascularization versus Integra. The collective long-term goal of our SBIR Phase I proposal and contemplated Phase II study is a DermiSphere prototype, ready for clinical trial, that triggers rapid dermal regeneration while avoiding skin contraction and scarring. When compared to currently available dermal substitutes, DermiSphere will induce faster wound closure, form more functional tissue, and lessen required procedures, reducing patient suffering and materially reducing health care cost. In this Phase I study we will prove the feasibility of our product by completing the following Specific Aims: (1) Demonstrate DermiSphere biocompatibility by testing its potential cytotoxicity in vitro by elution method, when formulated using bovine collagen. Criteria for Success: Biological response to DermiSphere is less than or equal to slight reactivity. (2) Demonstrate DermiSphere?s ability to support rapid dermal regeneration in a pilot in vivo swine full-thickness excisional wound model. Criteria for Success: Epidermal take ?75% on day 21 of the study and wound contraction ?20% and ?30% on days 14 and 60 of the study respectively. Our Phase II study will be a full- scale, full thickness excisional swine wound model to validate DermiSphere?s efficacy over Integra. Data from this study will also be used to improve formulation for both scale manufacturing and for pre-clinical safety and efficacy testing requirements. Demonstrating DermiSphere?s superior efficacy over Integra in a full-scale wound model is currently our first major strategic milestone. Achieving this milestone will sufficiently increase the equity value of FesariusTherapeutics Inc. to attract the capital needed to scale operations for increased manufacturing, FDA submission and commercialization.